[General education. 5. Economics. II].
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Biomedical subjects
Publications and source records attributed to H Shima.
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Protein phosphatase 2A alpha (PP-2A alpha) in one of the catalytic subunits of PP-2A, which is composed of catalytic and regulatory subunits. In fission yeasts, PP-2A mutants cause mitotic defects and strikingly different cell cycle phenotypes. In rat hepatocellular carcinomas, mRNA expression of PP-2A alpha was increased compared to that of normal hepatocytes. From these studies, PP-2A alpha has been thought to be involved in proliferation, and we expected that PP-2A alpha would decrease in HL-60 cells on dimethyl sulfoxide(DMSO)-induced granulocytic differentiation with decreased growth rate. In this study, we show that PP-2A alpha expression increases in HL-60 cells on DMSO-induced granulocytic differentiation, while PP-1 gamma, which is one of catalytic subunits of protein phosphatase 1, expression did not change significantly. These results suggest that PP-2A alpha may be involved in regulation of differentiation of hematopoietic cells.
We successfully stabilized severe hemorrhagic shock following traumatic liver injury by percutaneous transcarotid supraceliac aortic occlusion with a 5 Fr balloon catheter. Then we were able to perform transfemoral embolization therapy of the hepatic arterial bleeding source. Transient aortic occlusion using a balloon catheter appears to be a useful adjunct in select cases where stabilization of the patient is necessary to allow successful selective embolization of the bleeding source.
Okadaic acid (OA) is a specific and strong inhibitor of protein phosphatases 1 and 2A present in eukaryotes, and a potent promoter of carcinogenesis in mouse skin. In this study, we examined the mutagenicity of OA. OA did not induce mutations in S. typhimurium TA100 and TA98, with or without a microsomal metabolic activation system. However, it was strongly mutagenic to Chinese hamster lung (CHL) cells without a microsomal activation system, as shown using diphtheria toxin (DT) resistance (DTr) as a selective marker. Treatment of CHL cells with OA at 17.5 ng/ml induced 164 DTr mutants per 10(6) survivors. A plot of the mutation frequency against the OA concentration gave a concave curve, and the mutant frequency was calculated to be 5500/10(6) survivors/micrograms, with OA in the dose range of 10-15 ng/ml. This value was about 680 times that of ethyl methanesulfonate (EMS), and comparable to that of 2-amino-N6-hydroxyadenine, one of the strongest known mutagens. Elongation factor 2 (EF-2) obtained from 4 DTr clones was not ADP-ribosylated by DT fragment A. PCR-direct sequencing revealed that the hot spot of EF-2 for EMS mutagenesis in CHO-K1 cells, the first letter of codon 717, was not a hot spot for OA mutagenesis in CHL cells.
BACKGROUND: Ischemia-reperfusion (I/R) injury occurs in various situations, including transplantation, trauma, and shock. We previously reported that the synthetic beta-SQDG (18:0), which was derived from sulfoquinovosyl diacylglycerol of the sea urchin, possessed immunosuppressive effects, such as inhibition of T-cell responses in human allogenic human mixed lymphocyte reactions (MLR) and skin allograft survival in rats. beta-SQAG9 was synthesized from beta-SQDG (18:0) to improve structural stability in aqueous solution with the same biological activities to bind to CD62L (L-selectin) and CD62P (P-selectin) in vitro. We hypothesized that beta-SQAG9 might attenuate leukocyte rolling on the endothelium and neutrophil infiltration in which L-selectin and P-selectin are key molecules. We investigated the protective effect of beta-SQAG9 against hepatic I/R injury. METHODS: Male Lewis rats were divided into 6 groups: sham, control, and treatment. Rats in the control, and the treatment groups were subjected to hepatic ischemia for 30 minutes. They were injected with PBS or beta-SQAG9 at doses of 5, 10, 25, and 50 mg/kg into the penile vein immediately before reperfusion. To assess the damage to the hepatic parenchyma, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured and histological evaluation was performed at 6 hours after reperfusion. RESULTS: In the group treated with beta-SQAG9 at a dose of 10 mg/kg, AST, ALT, and LDH were significantly reduced, and the amount of neutrophil infiltration also was significantly reduced. CONCLUSIONS: Our data suggest that SQAG-9 (10 mg/kg) reduces the warm hepatic I/R injury.
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In this study, we investigated the optimal contents of branched-chain amino acids (BCAA) in a balanced amino acid infusion in laparotomized rats. The BCAA contents of four infusion solutions used were prepared to 22, 31, 40, and 49% of total amino acids, respectively. The amounts of essential amino acids except for BCAA were equal in all the solutions. Rats weighing about 240 g were infused with about 200 mg of nitrogen and 10 g of glucose daily for 7 days and evaluated for body weight change, nitrogen balance, plasma and urinary amino acid levels, and plasma constituent levels. The body weights of all the groups were approximately maintained during the infusion period. The nitrogen balance of the BCAA-31 group was more positive than that of the BCAA-22 group and was not different from those of the BCAA-40 and BCAA-49 groups. Plasma total-protein level of the BCAA-31 group was higher than that of the BCAA-22 group and was equal to those of the BCAA-40 and BCAA-49 groups. Even when the BCAA content in an amino acid infusion was increased, no abnormal elevation was observed in plasma BCAA levels. There were no differences in the other nutritional parameters among the four infusion groups. These results suggest that the BCAA contents in an amino acid infusion are enough at 31% of total amino acids for this injured rat model.
In this study, we investigated the optimal ratio of individual branched-chain amino acids (BCAA) in a balanced amino acid infusion in laparotomized rats. The total BCAA contents of four amino acid infusions were fixed at 31% of total amino acids. The weight ratios of individual BCAA (isoleucine:leucine:valine) in the solutions were 1:0.5:1, 1:1:1, 1:2:1, and 1:4:1, respectively. The laparotomized rats were infused with about 140 mg (experiment 1) and 100 mg (experiment 2) of nitrogen and 10 g of glucose daily for 7 days. In both experiments, no marked difference was observed in the mean cumulative 7-day nitrogen balance and the urinary 3-methyl-histidine levels of all the groups. The BCAA concentrations and the molar ratios of individual BCAA in plasma were disarranged by the infusion of the 1:0.5:1 and 1:4:1 solutions. The infusion of the 1:1:1 and 1:2:1 solutions tended, however, to allow the values to approach the preinfusion values. These results suggest that the optimal ratio of individual BCAA in an amino acid infusion lies between 1:1:1 and 1:2:1 for this injured rat model in total parenteral nutrition.
Effects of in vivo exposure to the synthetic polyprenoic acid, 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166) using 6 groups of rats treated simultaneously or individually with phenobarbital (PB) or with p,p'-dichlorodiphenyltrichloroethane (DDT) on the gap junctions of hepatocytes were examined by freeze-fracture analysis. Experimental groups were as follows: Group 1, basal diet alone; Group 2, E-5166 treatment; Group 3, 0.05% PB diet; Group 4, PB diet and E-5166 treatment; Group 5, 0.05% DDT diet; and Group 6, DDT diet and E-5166 treatment. E-5166 was given by gavage (40 mg/kg body weight, 3 times/wk). Experimental diets and E-5166 were started at 6 wk of age. All animals were sacrificed at 2 wk after the start of the experiments. The density of gap junctions in PB- or DDT-treated rats was higher and that in E-5166-treated rats was lower than that in controls. The density of gap junctions in rats given PB and E-5166-/or DDT and E-5166-treated rats was slightly increased when compared to controls. The average area of gap junctions in DDT- or PB and E-5166-treated rats was significantly smaller than in controls (p < 0.005), although no statistical differences were found among PB-, E-5166-, and DDT and E-5166-treated rats and controls. Unit area of gap junctions to membrane area in rats given E-5166, DDT, or PB and E-5166 was lower than in controls. However, the unit area of gap junctions in DDT and E-5166-treated rats did not differ from in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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The present study was designed to assess if the release of Na-K ATPase inhibitor (NKAI) after salt-loading is related to sympathetic nervous system in essential hypertension. Thirteen patients with essential hypertension were studied during low-salt diet (2 g/day) and then high-salt diet (20 g/day) for each 7-days period. Mean blood pressure (MBP), body weight, Na:K ratio in red blood cell (R-Na/K), plasma norepinephrine (PNE) and NKAI were measured on the last day of each period. NKAI was determined by the degree of the inhibition of dog kidney Na-K ATPase activity by deproteinized plasma. Patients were classified as "salt-sensitive" (SS) or "nonsalt-sensitive" (NSS) group by the MBP responses to salt-loading. With the high-salt diet, SS group showed more body weight gain, greater increase in R-Na/K and NKAI (SS; 8.0 +/- 1.0%, NSS; 2.4 +/- 0.8%, P less than 0.01) than NSS group. PNE showed no changes in SS group and decreased in NSS group (P less than 0.05). The increase of MBP was highly correlated with the rise of NKAI (r = 0.76, P less than 0.01). Moreover, the increase of NKAI was also significantly correlated with the changes of PNE (r = 0.62, P less than 0.05). These results suggest that the greater increase in blood pressure by salt-loading in SS patients can be attributed to the increase of NKAI, which might regulate the sympathetic nervous system as a result of increased intracellular sodium.
A 24-year-old man showed thyrotoxic symptoms with hypokalemic periodic paralysis. Serum thyroid hormone levels were high and thyrotropin (TSH) was undetectable. 123I-thyroidal uptake was suppressed. TSH-binding inhibitor immunoglobulin (TBII) was positive. After a month without any treatment, he became hypothyroid. Thyroid hormone level was decreased and TSH was increased to above the normal range. 123I-thyroidal uptake was increased. TBII activity was still positive. From the clinical findings, a diagnosis of silent thyroiditis was made. Sera obtained in the hypothyroid state revealed the presence of thyroid-stimulation-blocking antibodies (TSBAb), but there were no thyroid-stimulating antibodies (TSAb). These results suggest that the hypothyroidism in this patient was due to the presence of TSBAb with TBII activity.
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Cytologic, light and electron microscopic, and immunohistochemical studies were conducted on a case of elastofibroma. Aspiration cytology showed a characteristic "braidlike" or "fern leaf-like" structure. Immunohistochemically the accumulate was shown to be elastin. Transmission electron microscopy indicated electron-dense, granular aggregates surrounded by microfilaments and collagen, while scanning electron microscopy revealed balls with a ball-of-yarn-like structure consisting of small fibrils, probably of elastin. These structures are unique to this disease and useful for diagnosis.